The objective of this project is to evaluate the capabilities of various tissue lipases and esterases as early mediators in the interactions of animals with xenobiotics containing ester linkages. These enzymes are also used as models in studies of protein-ligand interactions. Through studies of the kinetic isotope effects in D2O we have been able to distinguish between general base catalysis and nucleophilic enhancement as the mechanism of the nonspecific lipase from rat pancreas.